Mutant KRAS, as well as other mutant driver genes and epidriver genes, is a dominant determinant of resistance to cancer therapeutics. The recent introduction of targeting therapies based on drugs that inhibit the kinase catalytic function of nodal points along the Ras/extracellular-signal-regulated kinase (ERK) and the phosphatidylinositol-3-kinase (PI3K)/Akt cascades is meeting with limited success. Against this background, recent evidence shows that the β-galactoside-binding protein (βGBP) molecule, a physiological PI3K inhibitor, is a potent inducer of apoptosis in KRAS-mutant cancer cells (along with other aggressive cancer cells of different genetic makeup) and that it is therapeutically effective in vivo. Absence of p53 or phosphatase and tensin homolog (PTEN) tumor suppressor function or added activating PI3K mutations does not affect βGBP function. In contrast to the concept of one drug against one target, βGBP operates through alternative physiological routes.
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